• Proteins are composed of amino acids linked together by peptide bonds.
• Each protein can be described in terms of its structural organization:
• Primary structure: Refers to the sequence of amino acids in the polypeptide chain, including the N-terminal and C-terminal ends of the molecule.
• Secondary structure: Involves the formation of alpha-helices and beta-sheets, which are local conformations stabilized by hydrogen bonds.
• Tertiary structure: Represents the overall shape of a single protein molecule. It includes protein domains, which are specific structural regions that confer specific functions to the protein, such as enzymatic activity.
• Quaternary structure: Describes the final shape of a protein, which is formed by the assembly of several protein molecules. These individual protein units are often referred to as protein subunits, as seen in the example of hemoglobin with its alpha2beta2 subunits.

Mnemonic: CAT HIPE 🐱

1. Complement and coagulation factors
2. Acute phase proteins: CRP (C-reactive protein), amyloid protein A, haptoglobin, fibrinogen
3. Transport proteins: haptoglobin, transferrin, ceruloplasmin, apolipoproteins
4. Hormones (proteohormones): calcitonin, PTH (parathyroid hormone), insulin
5. Immunoglobulins: IgG, IgA, IgM, IgE, IgD
6. Proteinase inhibitors: a1-antitrypsin, antithrombin III
7. Enzymes: amylase, lipase, cholinesterase

Mnemonic: HEI ABC HammerThrow, ps ICH LB DC

• coloidosmotic p. maintainance (mainly albumin)
• source for AA
• Buffer
• Transport
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💬 ICH LB DC
• Iron: hepcidin, transferrin, ferritin
• Calcium: calbindin
• Hormones
• Lipids: apoproteins A, B, C, E
• Bilirubin: albumin
• Drugs: cisplatine uses copper transport channels
• Trace elements: copper - ceruloplasmin
• Enzymes
• Immunity
• Hemostasis
• Heme metabolism

• Is used to separate proteins based on their electrical charge and size
• Used to identify which proteic fraction is modified & to orientate towards a syndrome, NOT the cause
• Based on their movement on an electrical field

• Albumin: 52-60% (1)
• Alpha-1 globulins: 3-5% (5)
• Alpha-2 globulins: 7-9% (4)
• Beta globulins: 11-14% (3)
• Gamma globulins: 16-20% (2)

IL1, IL6, TNF

binds to phosphocholine on pathogen → activates complement 📷

• quick incr. CRP
• ESP may be normal in first 24h
• CRP decr. more rapidly after treatment

• synthesized by the liver
• ↑ in acute + chronic inflammation
• platelet aggregation + clot formation

• genetic disorder → defective production of A1AT
• accumulation of abnormal A1AT in liver → liver disease
• Decr. activity in the lungs → panacinar emphysema 📷+ COPD
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centrilobular emphysema is seen in smoker, panacinar in imbalance betw. protease + protease-inhibitor (A1AT)

• avoiding of irritant inhalatin (smoking)
• infusion of A1AT
• liver + lung transplantation

• hereditary (Autosomal dominant)
• secondary: renal failure, nephrotic syd→ loss of ATIII

thrombosis 👣

• recurrent thrombosis + pulmonary embolism in hereditary form
• nephrotic syd → loss of Anti-Thrombin III → higher activity Factor II + X → thrombosis 📷

A tumor marker is a biomarker found in blood, urine, or body tissues that can be elevated by the presence of one or more types of cancer

• detectable in blood when malignant transformation occured
• precise identification of tissue malignancy

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• GI
• Liver
• Pancreas
• Breast, Cervic

• CA 15.3
• CEA
• BR27

• EGF
• Cathepsin D

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CA125

AFP (alpha-fetoprotein)

• CEA
• bHCG
• SCCA (squamous cell carcinoma antigen)
• cytokeratins (CYFRA)

PSA, free PSA

Calcitonin

• CEA
• CA (19.9)

AFP (alpha feto protein)

CEA

Ferritin

Hypercalcemia (osteolysis)

Alkaline phosphatase

Acid phosphatase

• gonads - testes + ovaries
• hematologic disease
• hepatic
• lymphoma
• melanoma
• neuroblastoma

• CNS tumors
• Neuroblastoma
• Neuroendocrine tumors (small cell lung)

→monitoring treatment of pulmonary+neuroblastoma

Galactosyl Transferase II

Paraproteins = Ig + light chain fragment

Protein M

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• ADH
• ACTH
• PTH

Dermatomyositis → AST, LDH, CK

Progressive muscular dystrophy (Douchenne) → in severe: AST, LDH, CK100UNL;; in carrier woman: CK+aldolase

Polymyositis: → CK

Malignant hyperthermia → CK, AST

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more details

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What is Dermatomyositis? What is the typical sign? What enzymes incr.?

• inflammation of CT of muscles + skin

• heliotropic rash 📷

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• ASAT, LDH, CK incr. (in acute phaseses)

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What's the definition of Progressive muscular dystrophy? What is a special form of it?

• progressive death of muscle tissue → replaced by fibrous tissue → progressive skeletal m. weakness)
• non-inflammatory, no nerve abnormalitiy
• Duchenne → X-linked recessive (mainly affecting boys)

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So what enzymes might be inc. in Carrier woman?

CK + Aldolase

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What else might be found in severe forms?

• CK 100x incr. UNL
• AST incr
• LDH incr

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So besides detection of carrier woman when do you wanna determine CK level?

diagnostic of risk before clinical signs present

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What is polymyositis? What enzymes are incr.?

• inflammation of many muscle groups

• CK

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How do you differentiate btw. progressive muscular dystrophy + polymyositis?

give cortisone → better? → myositis

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Whats the pathomechnaism of malignant hyperthermia?

i.e. halothane → trigger Ca efflux of intracellular depositis into myoplasma → sudden + sustained contraction

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What are the consequences (symptoms + signs, complications)?

• metabolic acidosis (incr. lactic acid)
• tachycarda + tachypnea
• muscle rdigitdy
• hyperthermia 41-42°

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What enzymes incr. confirm the dg. of malignant hyperthermia + how do you treat?

CK + AST (ASAT)

→ Ca2+ antagonists

reaction pyruvate + lactic acid

→ 📷

• LDH1: heart muscle
• LDH2: red blood cells
• LDH3: lungs
• LDH4: kidney, pancreas, placenta
• LDH5: liver and skeletal muscles

Megalob.: >10x UNL

Hemolytic: >2-5x UNL

→+AST might be slightly incr. in hemolytic

• low reticulocytes
• normochromic, macrocytic (megaloblastic)

• LDH2+3 incr. in leukemia
• VitB12 in biochem

• No response to therapeutic test (VitB12 administration)

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• low cholesterol in leukemia → bad prognosis

📷

• Collagen Type 1 → proliferation
• Bone alkaline phosphatase (BAP) → matrix maturation
• Osteocalcin → matrix mineralisation

acid phosphatase

• Osteoporosis (might be decr. or normal)

• Primary + Secondary Hyperparathyroidism
• Rickets / Osteomalacia (VitD defic) → secondary hyperparathyroidism → 2-3x UNL
• Hyperparathyroidism

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• Paget diseases

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• Osteoblastic tumor (i.e. metastasis from prostate, mamma)

metastatic prolipheration of osteoclasts → osteolysis (acid phosphatase incr)

⇒Osteolytic sarcoma (Ewig, reticulosarcoma)

→ ALP normal

• Mama + prostate Ca

• Gaucher disease

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outside layer: Apoprotein (ABCE), free Cholesterol, phospholipids

inside: cholesterol esters + TG

to transport hydrophobic lipids in the blood combined with hydrosoluble proteins

→Role Lipids in general: membranes, VitaminADEK-absorption, hormones,myelin sheath, organ padding

📷

1. Biliary acids: emulsification
2. Lipase: TG → FFA
3. nascent chylomicrons formation (ApoB) - 80%TG, <15%Cholesterol esters
4. Enter blood via lymph → ductus thoracicus
5. Receive Apo C II+E from HDL ⇒ mature chylomicrons
6. →Tissue → ApoC stimulates LPL → TG into FA,+ Cholesterol → into cells
7. Remnant Chylomicron → Liver: ApoE + LDL-R interaction

1. TG + CE into VLDL (ApoB-100)
2. LPL in peripheral tissue → VLDL into IDL by releasing TG into FA

3.1 IDL → LDL → carries CE to peripheral tissue (has LDL-R(ApoB) on surface) [3/4 ovary, testes + adrenal]

3.2 Part of IDL is directly taken up by the liver

1. TG + CE into VLDL (ApoB-100)
2. LPL in peripheral tissue → VLDL into IDL by releasing TG into FA

3.1 IDL → LDL → carries CE to peripheral tissue (has LDL-R(ApoB) on surface) [3/4 ovary, testes + adrenal]

3.2 Part of IDL is directly taken up by the liver

Synthesis:

• synthesized by liver + intestine
• liver makes ApoC+E → delivers to intestine

Reverse transport:

1. CE in tissue into FC
2. uptake by ABCA1-proteins ⇒ nascent HDL
3. Plasma: FC → CE by LCAT ⇒ mature HDL-3

→ into liver: Scavenger R B1

→ some of cholesterol esters transferred from HDL-3 to VLDL,IDL,LDL by CETP in exchange for TG ⇒ HDL-2 → to liver + cleaved by hepatic TG lipase → TG cleavage + free Apo A-1

⇒ Reformation of HDL3: ATP-binding cassete transporter A1 (ABCA1) → transfer cholesterol to pooly lipicated particles: pre-HDL or Apo-A1 → HDL3

• uptake Cholesterol from periph. → liver (reverse cholesterol transport)
• repository for ApoE+C for chylomicrons (+VLDL)
• competition with LDL for binding sites on membranes + prevention internalization LDL in arterial wall
• Stimulated Prostacyclin by endothelial cell → prevent thrombus

• Removal of Mp from arterial wall

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< 35/45 mg/dl

Implications → see below (hyper/dyslipidemia)

• Diseases associated with abnormal chemistry or metabolism of lipids:
• Obesity
• Atherosclerosis
• Diabetes Mellitus
• Hyperlipoproteinemia
• Fatty liver
• Lipid storage diseases
• Reference intervals:
• Total lipids: 500 - 800 mg/dL
• Cholesterol: 110 - 200 mg/dL
• Triglycerides: 50-150 mg/dL
• HDL-chol: >35; >45 mg/dl
• LDL-chol: 70 - 130 mg/dL

HDL3 + HDL2

Synthesis:

• synthesized by liver + intestine
• liver makes ApoC+E → delivers to intestine

Reverse transport:

1. CE in tissue into FC
2. uptake by ABCA1-proteins ⇒ nascent HDL
3. Plasma: FC → CE by LCAT ⇒ mature HDL-3

→ into liver: Scavenger R B1

→ some of cholesterol esters transferred from HDL-3 to VLDL,IDL,LDL by CETP in exchange for TG ⇒ HDL-2 → to liver + cleaved by hepatic TG lipase → TG cleavage + free Apo A-1

⇒ Reformation of HDL3: ATP-binding cassete transporter A1 (ABCA1) → transfer cholesterol to pooly lipicated particles: pre-HDL or Apo-A1 → HDL3

• HDL particles are classified:
• HDL2 (larger, less dense)
• HDL3 (smaller, denser).
• Each HDL particle consists of 4 apolipoproteins.
• HDL can contain apo A-I and apo A-II, or apo A-I alone.
• HDL2 primarily contains apo A-I, while HDL3 contains a combination of apo A-I and apo A-II.
• HDL particles less dense than HDL2 are enriched with apo E.

1. DM *
2. Hypothyroidism * (↑LDL + ↑IDL)
3. Nephritic/Nephrotic (↑VLDL product → ↑LDL)
4. Cholestatic liver diseases

→Abnormal Lipoproteins:

1. Lp-X
2. Lp-Y
5. Pregnancy
6. Diet rich in fat*

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1. Alcohol
2. Contraceptives oral

• I = familiar LPL def. / ApoCII def.
• IIa = familiar hyperCHOLESTEROLEMIA
• IIb, IV, V = familiar COMBINED hyperlipidemia
• III = Remnant Hyperlipidemia

Electrophoresis 📷

Ultracentrifugation 📷

LDL + VDL vice versa by Ultracentrifugation

Mutation → LDL-R (ApoB100-LDL-Chol-R)

• tendon xanthoma
• xanthelasma
• corneal arcus

CV-D

• Statins
• Niacin
• Bile acid sequestrants

Overproduction of B-100 → VLDL by the liver

no xanthomas!

moderate CV-D risk

1. Hypo-alpha-lipoproteinemia (Tangier + LCAT def.)
2. Hypo-beta-lipoproteinemia
1. A-beta-lipoproteinemia (homozygous)
2. Fam. hypo-beta-lipidemia (heterozygot of A-beta)
3. Chylomicron retention
3. Secondary hypolipoproteinemia

📷

• Tangier D: Mutation ABCA1
• LCAT def.

⇒ accumulation in Mp in body

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• Low + Abnormal HDL (spherical)
• opague cornea📷
• Proteinuria (free cholesterol) in renal microcirculation
• big + orange tonsils 📷
• Neuropathy
• Splenomegaly

Mutation in MTTP(microsomal TG transfer prot.) → ApoB deficiency → no CM, VLDL, LDL

• Low TG + Cholesterol (no CM, VLDL, LDL)
• Acantocytes
• Retina degeneration
• Normal at birth, later steatorrhea + growth delay

→ in heterozygots (Fam-hypo-beta): apoB+LDL only ↓50%

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• neonates → no intestinal chylomicron production
• LDL + VLDL ↓50%

• chronic cachexia (cancer)
• malabsorption
• Ig-disorders (Ig-lipoprotein-complexes)
• Protein-loosing enteropathy

• Random >200 mg
• Fasting >126

→ OGGT indicated

• Polydipsiam Polyuria, weightloss
• Glucosuria (if Gluc >180)

• HbA1c >6,3

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Measuring C-peptide can help to determine how much of their own natural insulin a person is producing as C-peptide is secreted in equimolar amounts to insulin. C-peptide levels are measured instead of insulin levels because C-peptide can assess a person's own insulin secretion even if they receive insulin injections, and because the liver metabolizes a large and variable amount of insulin secreted into the portal vein but does not metabolise C-peptide, meaning blood C-peptide may be a better measure of portal insulin secretion than insulin itself

1. DM
2. Pancreatitis
3. Acromegaly
4. Cushings
5. Diuretics*
6. Glucagonoma
7. Pheochromocytoma*
8. CRF *

• Rubella, CMV, Epstein Barr
• Hepatitis
• Alcoholic hepatitis
• Chemicals: Cholorform
• Toxic mushrooms
• yellow fewer
• Gallstones
• Prophyry Cutanea Tarda (see later)

• Chronic Hep - ↑IgG
• Biliary chirrhosis - ↑IgM
• Alcoholic hepatitis - ↑IgA

• Osmotic lysis (excessive water inflow → burst cell membrane)
• Degeneration (disruption of cell membrane

1. AST + ALT
• AST mitochondria
• ALT cytoplasms → ↑first (when membrane extens)
• small ↑ in cholestasis
2. LDH 5
3. Enzymes of the Krebscycle in mitochondria
1. OCT (ornithine carbamoyltransferase)
2. SDH (succinate dehydrogenase)
3. ICDH (isocitrate dehydrogenase)
4. GLDH (Glutamat dehydrogenase) in mitchondria

• No + degree of cells damage
• Vascularization of damaged tissue
• Existance of inflammatory barrier
• T1/2 of the enzyme

Non-specific

• Chronic Hep 5-20x
• Compensated cirrhosis 2-3x
• Liver Cirrhosis uncompensated parenchymal normal/slight↑

Esp. AL(A)T

• Acute viral hepatitis 10-50x

Esp. AS(A)T

• Activation of chronic hepatitis → ↑of AST/ALT coeff
• Alcoholic hepatopathy 5-10x
• Tumor - slight ↑
• Acute Necrosis due fungus + organic solvents intox 100x

• biomarker test
• six blood serum values → score ⇒ degree of liverdamage in patient with a variety of liver disease
• same prognostic value as liver biopsy

"Der 2. geborene(Alpha-2-macrogl) haftet (Haptoglobin) am ALTen (ALT) 1.geborenen APOthekter (ALPA1) GeGen (GGT) den er BILIard (Bili total) spielt. Der 2. geborene arbeitet bei der NASA (derivates), er heißt Gilbert und hat 2 acute Probleme (acute hep.+ac. inflamm. syd), die außerhalb der Leber stattfinden (extrahepatic cholestasis + hemolysis=pre+post-hepatic)"

• Alpha2-macroglublin
• Haptoglobin
• Apolipoprotein A1
• GGT
• Bili total
• ALT

"NASA"

• ActiTest - dg. necrotic inflamm. hepatitis
• SteatoTest - dg Steatosis
• NashTest - dg NASH inflamm.
• AshTest - dg. Alcohol liver diseases inflamm.

→likely FP (false pos) or FN (false neg)

→1-5%

• Acute hepatitis
• Acute inflammatory synd.
• Extrahepatic cholestasis
• Severe hemolysis
• Gilbert's synd

→ blood test postboned till feasible

• Alcoholism
• Biliary tract disease
• precipitated by: ↑Chylomicrons (TG>400mg/dl)

• ↑Amylase serum → 5-10x UNL
• ↑Amylase urine
• ↑Trypsin serum
• ↑Lipase urine+serum
• ↑Glucose
• ↑TG
• ↑Bili
• ↑Renal markers - Crea+Urea
• ↓Ca2+
• due to acute phase reaction → ↓albumin → ↓Ca
• Hydrolysis of Fat by Lipase → insoluble soaps

• ↑first 6h after onset
• remain ↑ for 2days
• remain longer in acute kidney insuff

• Hemoglobin
• Myoglobin
• binds Oxygen quicker than Hb
• ↑physical effort
• ↑muscular lesions (rhabdomyolysis)
• Heme containing enzymes in mitochondria involved in cellular respiration
• cytochromes
• cytochromoxidase

• Transferrin (Fe+Siderofilin)→ binds Fe3+
• Siderofilin → beta globulin, contain 1-3 Fe3+ molecules
• Receptors in Liver, Placenta, Erytroblasts+Reticulocytes
• ↑R in Iron def.
• ↓R in Iron overload + ↑Apoferritin (→storage)

• Fe3+ (non-heminic form) → Fe2+ (heminic form)
• active transport into mucosal cell
• can be stored here → as Ferritin (Fe3+)
• or as Fe2+ through Ferroportion out of the cell

→ conversion to Fe3+ + binding to Transferrin

• ↓ by Phosphates (milk products) + oxalates (green vegetables)
• ↑Vit C → Fe3+→Fe2+

• To Mitochondria → hemesynthesis
• Storage → 60% Ferritin(hydrosoluble) + 30% Hemosiderin (insoluble)
• Liver, Spleen, Bonemarrow → each get 30%
• ↓Ferritin in iron def. anemia (most sensitive marker)
• ↑Ferritin in hepatic inflammation, overload
• ↑Hemosiderin in iron overload (Hemochromatosis →prusian blue)

• tp1NP - Matrix prolif. → collagen type 1 synth.
• BAP (bone alkaline phosphatase)- Matrix maturation
• Osteocalcin - Matrix mineralization

"Der Wasser-Pro ist in der line (Hydroxyproline) vor der pyramide (pyridinoline) im schneidersitz (beta cross lap aka CTX) mit seinem Teleskop (C+N Telopeptide)

• Hydroxyproline (urine)
• Pyridinoline + Deoxypyridinoline
• C Telopeptide - CTX (beta cross lap) 📷
• N Telopeptide (urine + serum)
• Urinary calcium (not used anymore)

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no → dg by DEXA (dual energy xray absorptiometry)

⇒but used to check therapy response (biochem markers after max 3month, DEXA 1 year)

Increase

• Hemolysis (most Mg in RBC)
• Kidney lesions in prolonged salicilates + lithium treatment

Decrease

• Drugs: Aldosteron, Insulin, Diuretics with mercury
• Calciumgluconate - interference with testing methods

"Das aggro(acromeg) kid (kidney insuff) mit dem riesen boner dick (bone tumor+VitD) hat keinen hypoparathyroidgland. Deswegen geht er zu Rick ins krankenhaus der im Coma liegt weil er zu viel insulin gespritzt hat und klaut ihm seinen Hyperparathyroid gland."

• kidney insuff (cant be excreted)
• hypoparathyroidism (no stimulation of urinary excretion via PTH)
• ↑VitD (incr. reabsorption)
• Acromegaly (incr. reabsorption due to GH stimulation=
• bone tumor (incr. bone loss)

• Hyperparathyroidism (incr. excretion)
• Rickets (decr. VitD activity on reabsorption)
• Diabetic coma (treatment??→see below)
• Hyperinsulinemia (Stimulation of glycolysis → ↑formation of phosphorylated carbohydrate compounds in liver+skeletal muscle)