Upload
others
View
1
Download
0
Embed Size (px)
Citation preview
CASE 1
CASE 1
A 22-year-old female restricted vegetarian was seven months pregnant. She had been experiencing
frequent headaches and extreme fatigue and weakness. Following an episode of syncope, she made an
appointment with her doctor. Upon examination, her physician noted that his patient had an elevated
heart rate and pallor of the skin, mucous membranes and nail beds.
The following peripheral blood tests were performed:
Hb- 11 (13-18g/dL)
Ht – 35 (40-54%)
MCV- 75 (80-95fL)
MCH- 22 (27-32pg)
MCHC-31 (32-36g/dL)
RBC- 3.8 (4.5-6 T/L)
WBC- 5.6 (4-10 G/L)
PLT- 345 (150-450G/L)
Iron – 45 ( 50-180μg/dL)
TIBC- 580 (280-550 μg/dL)
Bilirubin – 5 ( 3-10mg/L)
1. What is TIBC and what does it describe ?
2. What is the reason for tachycardia and pallor?
3. How do you explain decreased MCV ?
4. What is the reason of low iron concentration in the blood?
5. How do you explain the prevalence of anemia in chronic inflammation.
A N E M I A - DEFINITION
Anemia is defined as a reduction in one ore more of the
major red blood cell measurements:
• Hb concentration
• Hematocrit
• RBC count
WHO criteria for anemia is:
Hb < 14 g/dl in men
< 12 g/dl in women
RED BLOOD CELLS
morphology
MEAN CORPUSCULAR VOLUME ( MCV)
80-94 fL (m3)
< 80 microcitic; > 100 macrocytic
MEAN CELL HEMOGLOBIN in RBC ( MCH)
27-34 pg
MEAN CELL HEMOGLOBIN CONCENTRATION
(MCHC)
31-37 g/dL normochromic
<31 g/dL hypochromic
Approach to anemia
anemia
check MCV
MCV < 80
microcytic
anemia
MCV 80 - 100
normocytic
anemia
MCV > 100
macrocytic
anemia
CLINICAL CONSEQENCES OF
ANEMIA I
S y p t o m s a r e d u e t o h y p o x i a
• NORMAL Hb CONCENTRATION:
women: 12-16 g/dL
men: 14-18 g/dL
optimum oxygen delivery occurs with Hb 15 g/dL
CLINICAL CONSEQENCES OF
ANEMIA II
• Fatigue
• Somnolence (sleepiness)
• Iintolerance to cold
• Pallor of skin and mucous membranes
• Hypotension due to hypoxia (vaodilators: ↑H+, ↑ lactate, ↑ CO2)
• Tachycardia (angina, arrhythmia, palpitation)
• Ringing in the ears
• Headache
• Dispnea & dyspnea at rest
• Lethargy
• Confusion
• Dizziness
MICROCYTIC ANEMIA
MCV < 80fL
• Reduced hem synthesis (syderoblastic anemia):
iron deficiency anemia (IDA)
lead exposure (rare nowedays)
porphyria ( deficency of certain enzymes in hem synthesis )
• Reduce globin production (thalassemia)
• Hemolytic anemia (e.g. hemoglobinopathies, membrane defects)
IRON DEFICIENCY ANEMIA
Iron deficiency anemia is the most
common anemia, particularly in women
and children
Approximately 20% of all women have
anemia
IRON METABOLISM
ABSORPTION
• Apoferitin – is a protein which helps iron to
absorbed in the mucosa of the proximal
small intestine (mainly duodenum)
• 5-10% of daily intake is only absorbed
IRON METABOLISM - STORAGE
MAJOR STORAGE DEPOT IS THE LIVER
Stored as ferritin and hemosyderin
F E R R I T I N
• primary storage, stored in cell cytoplasm
• release for heme synthesis
H E M O S Y D E R I N
• major long term storage form of iron in lysosomes
• slow release
IRON METABOLISM –TRANSPORT
T R A N S F E R I N
• major iron transport protein in blood (95%)
• about 30% saturated with iron (up to 50% - IDA)
• most iron bound to transferrin comes from the
breakdown of hemoglobin in liver and slpeen
• total transferrin present in plasma to bind the iron
present in plasma = TOTAL IRON-BINDING
CAPACITY (TIBC) (TIBC is the blood’s capacity to bind iron
with transferin) = iron level + LIBC (latent iron binding capacity)
IRON LOSS OF THE BODY
• Daily exfoliation of intestinal mucosa
• Menstruation
• Nails and hair cut
IRON METABOLISM
• Iron level: 55-180 ug/dL
• Transferin : 200-400mg/dL
• TIBC: 250-500ug/dL
IRON – DAILY INTAKE
• Women – 20 mg
• Men – 10 mg
• Pregnant women – 30 mg
• Infant- 10 mg
• Children (1-6 year) – 5-8 mg
• Youth (13-19 year) – 15 mg
IRON RICH FOOD
Fe 2+
• Liver
• Beef
• Lamb
• Pork
• Veal
• Chicken
• Fish
Fe 3+
• Green leafy vegetables
• Beetroot
• Prunes
IRON DEFICENCY - SYMPTOMS
• brittle nails and hair
• spoon nails (koilonychia)
• mucosal atrophyy: glossitis (smooth
erythematous tongue), dysphagia, cheilitis
ETIOLOGY OF IDA
• Blood loss ( 80%)
• Dietary deficiency
- cause in developing countries
- infants, pregnancy, adolescence
• Malabsorbtion
• Chronic inflammatory disorders
ANEMIA OF CHRONIC DISEASE
CAUSES
-chronic infections (often in children)
- chronic inflammatory disorders (obesity, uremia, autoimmune diseases)
-chronic inflammation (elder people)
- neoplastic disorders
- autoimunne disorders
PATHOMECHANISM
1. Decreased iron absorption from GI tract
2. Decreased release of iron from macrophages from RE system
3. Relative reduction in EPO (cytokines) and impaired marrow response
4. Shortened RBC survival
CASE 2
CASE 2
A 70-year-old woman presented with progressive weakness and fatigue. The symptoms had begun
about a month earlier and she no longer felt well enough to do her housework or take her daily walk.
Although her breathing was normal at rest, she was too short of breath to walk more than two or
three blocks. She had no history of recent bleeding, juandice, fever, anemia or heart disease. She had
not been exposed to medications. She had not abused alcohol and had no previous hospitalization
Finding on the physical examination were unremarkable except for mild tachycardia at rest (96), a
blood pressure of 146/84 mm Hg, pallor and the stool was negative for occult blood.
The following peripheral blood tests were performed:
Hb- 8,4 (13-18 g/dL)
Ht – 32 (40-54%)
MCV- 103 (80-95 fL)
MCH- 35 (27-32pg)
MCHC-37 (32-36 g/dL)
RBC- 3,3 (4.5-6 T/L)
WBC- 3,9 (4-10 G/L)
PLT- 110 (150-450 G/L)
Iron – 150 ( 50-180 μg/dL)
TIBC- 525 (280-550 μg/dL)
Bilirubin – 11 ( 3-10 mg/L)
Bleeding Time ( Duke) - 6 (2-5min)
1. What is the explanation for her weakness, fatigue and breathing problems?
2. What is the most probable reason for low level of RBCs, WBCs and platelets?
3. What additional blood test would be helpful ?
4. How do you explain the out of range bilirubin level ?
5. How do you explain the prolonged bleeding time?
MACROCYTIC ANEMIA
MCV > 100fL
• Abnormalities of DNA metabolism
- vitamin B12 deficiency (pernicious anemia)
- folate deficiency
- drugs (metothrexate, contraceptives)
• Lipid abnormalities
- liver disease
• Alcohol abuse (poor diet, GI complications)
MEGALOBLASTIC ANEMIA I
Abnormalities in the absorption or metabolism of folate
or cobalamine ( vit. B12).
The result is that DNA synthesis is inhibited and the cell
cycle is slowed down during erythropoesis.
Hemoglobin synthesis in cytoplasm is unchanged but
erythriblasts increase in size (megaloblasts; MCV>100fL)
and oval erythrocythes pass into the blood.
There is normal cytoplasm synthesis but, nucleus
synthesis is delayed.
MEGALOBLASTIC ANEMIA II
The formation of granulocytes and
megacaryocytes (platelets) is also disturbed
There is premature destruction of megaloblasts in
bone marrow (inefficient erythropoesis) and
shortened life-span (premature hemolysis)
COBALAMINE ( VITAMIN B12) I
Must be taken up by humans in their food.
Foods rich in cobalamine: mostly animal food: meat,
eggs, milk, fish
Daily requirement 1-5 g
Main storage – liver (enough for 3 years)
Normal absorption of vit B12 needs intrinsic factor,
produced by the gastric mucous (parietal cells).
Autoimmune disorder- antibodies vs. intrinsic factor or
parietal cells is called pernicious anemia
Site of absorption - ileum
COBALAMINE ( VITAMIN B12) II
METABOLIC FUNCTION
In cells it is metabolized to methylocobalamine
Methylcobalamine is needed to demethylation of
methyltetrahydrofolate to tethrahydrofolate (THC)
Methylcobalamin
N5-methyl-THF THF DNA synthesis
homocysteine methionine
Fatty acids synthesis (conversion of methylmalonyl CoA
to succinyl CoA).
COBALAMINE ( VITAMIN B12) III
DEFICIENCY
Intrinsic factor deficiency (pernicious anemia)
Too little uptake with food (strict vegetarian diet)
Competition for cobalamine ( broad fish tapeworms:
(Diphyllobothrium latum) in the intestinal lumen)
The symptoms of cobalamine deficiency may occur only
after years of blocked supply (great liver storage)
FOLATE I
Necessary for the synthesis of DNA (the only source of
thymidin)
Folate deficiency inhibits the rate of formation of rapidly
proliferating cells for example during erythropoesis and tumor
formation.
Daily intake – 50 g
Food source – leafy fresh green vegetables (overcooking food
destroys folate), red meats (liver); must be provided by dietary
sources
Absorption – duodenum, upper jejunum
Main storage – liver ( 2-3 months)
FOLATE DEFICIENCY
Too little folate uptake with food (fresh green
vegetables)
Increased requirement (pregnancy)
Malabsorbtion ( diseases of the small intestine e.g.
Celiac disease)
Inhibition of folate synthesis caused by cytostatic
chemotherapeutics (methotrexat, fluorouracil,
aminopterin)
Low absorption (contraceptive pills)
Folate deficiency is more commonly
encountered in clinical practice
Megaloblastic anemia is often seen as
malnutrition in the elderly, alcoholics ,
teenagers and in pregnancy
MEGALOBLASTIC ANEMIA - SYMPTOMS
H E M A T O L O G I C A L
Megaloblasts MCV →>100, reduced Hb, RBC, Ht
G A S T R O I N T E S T I N A L
Severe glossitis (inflamed red and painful tongue)
Diarrhea
N E U R O N A L (only vit. B12 deficiency → reduced fatty acids
synthesis → disturbed myelin synthesis → neuronal symptoms
Dementia
Ataxic gait (unsteady)
Psycholgical disturbances
Sensory disorders
CASE 3
CASE 3
44-year-old patient, 4 years treated with chronic immunosuppressive drugs, because of systemic lupus
erythematosus, came to the hospital with intensified following disorders such speech disorders and jaundice.
On aadmission the patient, has no circulatory and respiratory problems and no clinical signs of infection. CT
excluded bleeding into the central nervous system.
The following peripheral blood tests were performed:
Hb- 8,4 (13-18 g/dL)
Ht – 37 (40-54%)
MCV- 84 (80-95 fL)
MCH- 29 (27-32 pg)
MCHC- 34 (32-36 g/dL)
RBC- 3,3 (4.5-6 T/L)
WBC- 8.8 (4-10 G/L)
PLT- 160 (150-450 G/L)
Reticulocytes – 7.1 (0.2-2%)
Iron – 100 ( 50-180 μg/dL)
Bilirubin – 19 ( 3-10 mg/L)
LDH - 250 (140-240 U/l)
Free Hb - 85 (trace 3-10 mg/dL)
Haptoglobin - 0,4 (0.5-2 g/L)
1. Why free Hb and haptoglobin were tested?
2. What is the link between systemic lupus erythematosus and anemia?
3. What are the reasons of hemolytic anemia?
4. Why bilirubin and LDH were tested?
5. How do you explain high reticulocytes count in this case ?
6. What are the compensatory mechanisms of anemia?
Systemic lupus erythematosus (SLE) is an autoimmune
disease.
In this disease, the body's immune system mistakenly
attacks healthy connective tissue (antibodies)
Connective tissue is present in our entire body, therefore the
symptoms affect many organs
Antibodies affect the skin, joints, kidneys, brain, RBCs,
PTLs and other organs.
LUPUS ERYTROMATOUS
HEMOLITIC ANEMIA
Hemolytic anemia is a form of anemia due to hemolysis.
Hemolysis is the rupturing of erythrocytes and the release of their contents (Hb) into surrounding fluid (blood plasma).
The abnormal breakdown of (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular).
RBC life span below 100 days (as little as several days = definition of hemolysis)
HEMOLITIC ANEMIA
CORPUSCULAR HEMOLYTIC ANEMIA
(MAINLY INHERITED). RBCs are removed from peripheral blood by extravascular hemolysis
• spherocytosis, ovalocytosis, sicle cell anemia, talasemia
EXTRACORPUSCULAR HEMOLYTIC ANEMIA (MAINLY ACQIRED). RBCs are removed from peripheral blood by intravascular hemolysis
• blood group mismatches, malaria, snake poisoning, mechanical cause (e.g. artificial heart valves), viral infection
EXTRAVASCULAR HEMOLYSIS
INTRAVASCULAR HEMOLYSIS
JAUNDICE
Jaundice is an excess of bilirubin in blood
Bilirubin is a breakdown product of hemoglobin that it is
normally excreted into the bile
In hemolytic anemia increased red blood cell destruction
leads to the increased release of free Hb and increased
production of bilirubin
The liver is not able to remove bilirubin so fast, leading to
pigmented skin and the whites of the eyes with the
characteristic yellowish color indicative of jaundice
1. CENTRAL MECHANISMS
Increased cardiac output
Increased heart rate (tachycardia)
2. PERIPHERAL MECHANISMS
Vasodilation (reduced peripheral resistance)
Lowering blood viscosity
Increased blood flow through the heart and brain (activation of the sympathetic
nervous system →vasopresin→ relaxation of cerebral and coronary arteries and constriction of other
artheries)
Decreased blood flow through the kidneys, muscles, skin
Increased erythropoetin synthesis
3. ERYTHROCYTE MECHANISM :
Increased synthesis of 2,3 - DPG (bifosfoglicerynian) →easier oxygen transfer to the
tissues
4. TISSUE MECHANISMS :
Increased extraction of oxygen
Increased anaerobic methabolism
ANEMIA – COMPENSATORY MECHANISMS
CASE 4
CASE 4
56 year old man suffering from diabetes, was admitted to hospital because of chronic fatigue, somnolence and
poor concentration. In contrast to the previous period he could not focus his attention on anything , which
greatly hinder his business. During the night, he gets up 2-3 times to urinate. Do not drink alcohol and smoke
cigarettes.
The following peripheral blood tests were performed:
Hb - 11 (13-18 g/dL)
Ht – 32 (40-54%)
MCV - 85 (80-95 fL)
MCH - 30 (27-32 pg)
MCHC - 36 (32-36 g/dL)
RBC- 3.8 (4.5-6 T/L)
WBC- 8.1 (4-10 G/L)
PLT- 190 (150-450 G/L)
Urea – 123 (15-40 mg/dL)
Creatinin – 2,8 (0.6-1.3 mg/dL)
pH - 7.38 (7.35-7.45)
Bicarbonate – 27 (23-27 mmol/L)
Na – 142 (135-145 mmol/L)
K – 4,4 (3.8-5.0 mmol/L)
24 h urine collection – 3L (1,5-2.0 L)
Proteinuria – 500 mg/dL ( < 30 mg/ day)
Glycosuria – 200 mg/dL ( 0 mg/dL)
1. How do you explain the elevated serum creatinine and urea?
2. What is the patient daily loss of protein ?
3. How do you interpret anemia in this particular case. Is it normocytic, makrocytic or microcytic anemia?
4. How do you interpret polyuria, proteinuria and glycosuria?
5. Is diabetes melitus cause of renal failure or anemia?
NORMOCYTIC ANEMIA
MCV 80-100fL
Acute blood loss
Aplastic anemia
Chronic renal failure (EPO)
Hemolytic anemia (normocytic & microcytic)
DIABETIC NEPHROPATHY Chronic loss of kidney function due to diabetes mellitus
Diabetic nephropathy begins because of long lasting elevated
blood glucose levels which damage arterioles and nephrons
This implicated multiple changes in kidneys:
- reduced GRF
- proteinuria
- glycosuria
- polyuria (due to osmotic diuresis)
- elevated serum urea and creatinin level
- anemia
- water and electrolytes disturbances
- disturbances of acid-base balance
ANEMIA OF CHRONIC DISEASE PATHOMECHANISM OF CHRONIC RENAL FAILURE IS
CONNECTED WITH CHRONIC INFLAMMATION
CAUSES
-chronic infections (often in children)
- chronic inflammatory disorders (obesity, uremia, autoimmune diseases)
-chronic inflammation (elder people)
- neoplastic disorders
- autoimunne disorders
PATHOMECHANISM
1. Decreased iron absorption from GI tract
2. Decreased release of iron from macrophages from RE system
3. Relative reduction in EPO (cytokines) and impaired marrow response
4. Shortened RBC survival